The basic principles of neuropharmacology 2 Flashcards
Medicine
Practices and procedures used for the prevention, treatment or relief of symptoms of disease or abnormal conditions
Term may also refer to a legal drug used for the same purpose
Drug
Any substance (other than food) that is used t prevent, diagnose, treat or relive symptoms of a disease or abnormal condition
- can also affect how the brain and he rest of the body work: e.g changes in mood, awareness, thoughts and feelings or behaviour
Psychotropic agents
Drugs that influence behaviour
Action of drugs on neural target
- the initial target of a drug determines the cells and circuits on which the drug acts and at the same time the potential efficiency and side effects
- the initial binding of a drug to its target is only the beginning of a signalling cascade that affects the behaviour of cells, neural circuits and animals
Pharmacodynamics
- gkr, medicine and power
Drug of action —> pharmacological effect —> response - “what a drug does to the body”
- the ability of a drug to produce an effect on an organism is dependent on the underlying mechanisms of drug action
Affinity, efficiency, concentration-response relationships, spare receptors and amplification
Pharmokinetics
- gkr, medicine and movement
Administration —> circulation —> (brain, kidney, liver) —> clearance - “what the body does to a drug”
- the time course of a drug in the body
Pharmokinetis and bioavailability
Ability of a drug to produce an effect on an organism is dependent on a many of it’s properties (& its mechanism of action) from its stability to its elimination —> its bioavailability
Stages of pharmokinetis
- Route of administration
- Release/liberation
- Absorbtion (dosing regiments)
- Distribution (compartments)
- Metabolism (metabolite kinetics, clearance)
- Excretion (clearance)
Enteral administration
through intestine
- oral administration —> relatively slow onset if action
- sublingual/buccal/rectal
Parenteral administration
Other routes including
- intravenous
- intramuscular
- subcutaneous
- intraperitoneal (into peritoneal-abdominal cavity)
- intracerebroventricular
- intracerebral delivery (into brain parenchyma)
Oral bioavailability - absorption
Most of the drug are absorbed within the duodenum/jejunum of the small intestine
- villi increase surface area
- highest concentration of villi on duodenum/jejunum
- lines with epithelial cells
- supportive network of capillaries draining the portal vein
Drug absorption processes
- passive diffusion
- convective absorbtion
- active transport
- facilitated transport
- ion pair formation
- pinocytosis
Is absorption the disappearance of drug from its site of administration or the appearance of drug in the general circulation?
absorption is the disappearance of drug from its site of administration
Drug absorbtion depends on intestinal motility:
- food
- exercise
- disease
- drugs
- time of day
Oral bioavailability - first pass metabolism
Most venous outflow from stomach, small & large intestine enters the portal vein en route to the liver
- goes into major body fluids e.g plasma
- metabolism: mainly liver (cytochrome P450 enzymes), prodrugs (in active until metabolised)
- excretion: renal and faecal elimination
Bioavailability is affected by binding to plasma proteins:
- many drugs bound to circulating plasma proteins such as albumin
- only free drugs can act as receptor site
- highly protein bound drug: >95% bound
> 95 % bound
- thyroxine
- warfarin
- diazepam
- frusemide
- heparin
- imipramine
- amitriptyline
> 90% but <95% bound
- glibenclamide
- phenytoin
-propranolol - sodium valproate
Bioavailability is affected by barriers:
- dependent on no. Of cascades/ no. Of events
- decided at every step wether it will reach the liver
- whether it will cross blood brain barrier
- important to determine doses, how much is actually going to the brain?
Getting drug to the brain - bioavailability:
- bioavailability of a drug determines how much administered actually reaches the target
- influences by absorbtion of the drug
- affected by metabolism and secretion
- affected by binding of drug to plasma proteins -> makes the drug unavailable to bind to its target
- ability to penetrate BBB/cell membranes
Dose
Amount of drug administered
Dosing interval
Time between drug dose and administration
Cmax
Peak plasma concentration of drug after administration
Tmax
Time to reach Cmax
Vol of distribution
Apparent volume in which drug is distributed (relates to drug concentration in plasma to drug amount in the body)
Concentration
Amount of drug in a given volume of plasma
Elimination half-life
The required concentration of drug to reach half its original value
Area under the curve
Integral of the concentration-time curve (After a single dose or in steady state)
Clearance
Volume of plasma cleared of the drug per unit of time
Fundamentals of Pharmokinetics
Volume of distribution
Clearance
Elimination half-life
